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Artemisia annua
Frontiers in Bioengineering and Biotechnology · 2021 · IF 5.89

High-Level Patchoulol Biosynthesis in Artemisia annua L.

Fu Xueqing,Zhang Fangyuan,Ma Yanan,Hassani Danial,Peng Bowen,Pan Qifang,Zhang Yuhua,Deng Zhongxiang,Liu Wenbo,Zhang Jixiu,Han Lei,Chen Dongfang,Zhao Jingya,Li Ling,Sun Xiaofen,Tang Kexuan

Terpenes constitute the largest class of secondary metabolites in plants. Some terpenes are essential for plant growth and development, membrane components, and photosynthesis. Terpenes are also economically useful for industry, agriculture, and pharmaceuticals. However, there is very low content of most terpenes in microbes and plants. Chemical or microbial synthesis of terpenes are often costly. Plants have the elaborate and economic biosynthetic way of producing high-value terpenes through photosynthesis. Here we engineered the heterogenous sesquiterpenoid patchoulol production in A. annua. When using a strong promoter such as 35S to over express the avian farnesyl diphosphate synthase gene and patchoulol synthase gene, the highest content of patchoulol was 52.58 μg/g DW in transgenic plants. When altering the subcellular location of the introduced sesquiterpene synthetase via a signal peptide, the accumulation of patchoulol was observably increased to 273 μg/g DW. This case demonstrates that A. annua plant with glandular trichomes is a useful platform for synthetic biology studies.

CAS / MDL: 5986-55-0
研究领域: 植物学 · 合成生物学 · 药用植物遗传工程
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2022 ·Vol. 414 ·期 29 ·8447-8461 · IF 4.478

Ti3C2(OH)x-assisted LDI-TOF-MS for the rapid analysis of natural small molecules

Li Hui,Ma Chunxia,Gao Meng,Li Yong,Xie Lei,Zhao Dantong,Zhang Runhao,Zhang Guanhua,Li Wenhan,Rong Rong,Kong Biao

The inhomogeneous distribution of co-crystallized analytes and the traditional organic matrices as well as the intensive background interference in the low molecular weight range hinder the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in the analysis of small-molecular compounds. New two-dimensional material MXene (e.g., Ti 3 C 2 ) exerts better hydrophilicity, homogeneity and repeatability, and higher laser desorption efficiency, as well as less background interference than traditional organic matrices and other nanomaterial matrices such as titanium oxide, graphene, and gold nanostructures. This study was aimed to design Ti 3 C 2 matrix with abundant hydroxyls on its surface, enhance the stability of this hydroxyl-rich Ti 3 C 2 (Ti 3 C 2 (OH) x ), and evaluate the analytical performances of Ti 3 C 2 (OH) x -assisted laser desorption/ionization time-of-flight mass spectrometry (LDI-TOF-MS) for small-molecular natural compounds in complex samples. The developed Ti 3 C 2 (OH) x showed the distinct advantages such as minimum background interference, high peak intensity (~10 5 ), high salt (0.6 M) and protein (0.5 mg/mL) tolerance, good repeatability (relative standard deviation<20%), and good stability after eight months of storage. Ti 3 C 2 (OH) x -assisted LDI-TOF-MS analysis could be used to rapidly identify Artemisia annua (a world-famous traditional Chinese medicine) and quantify the contents of the main chemical ingredients (oxymatrine (OXY) and matrine) of Compound Kushen Injection (CKI). Interestingly, the content of OXY in CKI could be accurately quantified by Ti 3 C 2 (OH) x -assisted LDI-TOF-MS, and there was a good linear relationship ( R 2 −0.9929), a low limit of detection (400 pg), and a low limit of quantification (600 pg) of OXY. Taken together, the rapid and accurate analysis of small-molecular natural compounds in complicated samples could be achieved by the Ti 3 C 2 (OH) x -assisted LDI-TOF-MS analysis. Graphical abstract

研究领域: 分析化学 · 中药学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Applied Research on Medicinal and Aromatic Plants · 2021 · IF 3.4

Periodic peristalsis enhanced artemisinin extraction in high solids of Artemisia annua

Jintong Zhang,Lan Wang,Hongzhang Chen

Artemisinin extracted at low solid loading causes low product concentration and high organic solvent usage. In this study, extraction in high solids of Artemisia annua by periodic peristalsis was proposed to increase the concentration of artemisinin and improve the extraction efficiency. The results showed that the artemisinin yield, extracted from leaves of Artemisia annua , increased by 33.9 %–46.5 % in periodic peristalsis extraction (PPE) compared with hot maceration extraction (HME). Based on the lower T2 relaxation time and the higher peak height of pools of solvent, periodic peristalsis could enhance solvent penetration effectively in porous media. Additionally, since the properties of capillary solvent were highly related to the diffusion coefficient (Pearson correlation coefficient > 0.98), periodic peristalsis improved the diffusion coefficient mainly by promoting the penetration of capillary solvent, which resulted in an increase in high solids extraction efficiency. Therefore, periodic peristalsis treatment could be an effective technology to improve natural product extraction performance in high solids.

研究领域: 植物学 · 药用植物研究 · 提取技术
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GREEN CHEMISTRY · 2017 ·Vol. 20 ·期 3 ·713-723 · IF 9.125

Ultrasonic assisted extraction of artemisinin from Artemisia Annua L. using monoether-based solvents

Yongqiang Zhang,Phongphat Prawang,Chunshan Li,Xiangzhan Meng,Yu Zhao,Hui Wang,Suojiang Zhang

Artemisinin is a kind of natural antimalarial drug exhibiting low toxicity and a very fast action against malaria. Solvent extraction is the most widely used method to separate artemisinin from the Chinese medicinal herb Artemisia annua L. In this study, a series of monoether-based solvents were investigated to extract artemisinin, and propylene glycol methyl ether (PGME) was found to be the most appropriate one for this extraction. Ultrasonic irradiation was demonstrated to be able to assist artemisinin extraction. Influence of extraction conditions, including liquid/solid ratio, extraction temperature, ultrasonic time, and ultrasonic power, on the extraction efficiency were discussed by single-factor experiments, and the main influencing factors were optimized by response surface methods. The extraction mechanism was explored using spectroscopic characterizations, and kinetics of this process was also studied. Results indicated that ultrasonic assisted extraction using PGME had faster extraction rate than conventional solvents, and ultrasonic could significantly enhance mass transfer. Compared with conventional extraction, the process developed here exhibited a higher efficiency (13.79 mg g−1vs. 13.29 mg g−1) and shorter extraction time (decreased from 8 h to 0.5 h) at a relatively low temperature. In addition, PGME had low toxicity and volatility, making the extraction process more safe and reliable. Therefore, this proposed method demonstrated that PGME-based ultrasonic assisted extraction is a rapid, efficient, simple and safe technique for natural product extraction.

研究领域: 药用植物学 · 天然产物化学 · 中药学
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BIOLOGIA PLANTARUM · 2011 ·Vol. 55 ·期 4 ·669-674 · IF 1.582

Singlet oxygen as a signaling transducer for modulating artemisinin biosynthetic genes in Artemisia annua

Zeng Q. -P.,Zeng X. -M.,Yang R. -Y.,Yang X. -Q.

Although crosstalk between cytosolic and plastidic terpenoid pathways has been validated in many plant species, we report here for the first time a striking elevation of the nucleus-encoded artemisinin biosynthesis relevant DBR2 mRNA following the incubation of plants with fosmidomycin (FM). FM decreased singlet oxygen ( 1 O 2 ) scavengers such as β-carotene and α-tocopherol and subsequently invoked 1 O 2 burst. The treatment of plants with fluridone (FD) neither decreased α-tocopherol content nor triggered 1 O 2 emission. In conclusion, FM can up-regulate 1 O 2 -sensitive nuclear genes responsible for artemisinin biogenesis by mitigating the accumulation of plastidic scavenging terpenoids, thereby eliciting 1 O 2 generation and initiating 1 O 2 retrograde signaling.

CAS / MDL: 59756-60-4
研究领域: 植物生物化学 · 分子遗传学 · 植物化学
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PLoS One · 2025 ·Vol. 20 ·期 5 ·e0322835 · IF 2.6

The plant matrix of Artemisia annua L. for the treatment of malaria: Pharmacodynamic and pharmacokinetic studies

Fujie Xu,Xiaohang Shan,Jialin Li,Jing Li,Jiqiao Yuan,Daozeng Zou,Manyuan Wang

Artemisinin-based combination therapies (ACTs) constitute the principal strategy for combating malaria in contemporary times, and research into the multifaceted components of Artemisia annua L. ( A. annua ) has garnered widespread interest among scientists. The aim of this study was to prepare A. annua extracts (nACTs) and to explore whether nACTs have higher bioavailability and efficacy than artemisinin (ART) alone due to its multiple bioactive components. Initially, the in vivo antimalarial activity of nACTs was evaluated by two murine malaria models. The results revealed that the antimalarial effect of nACTs was about 10-fold higher than that of ART alone when administered at the same dosage of ART. Then, we analyzed the pharmacokinetic characteristics of nACTs in rat plasma. Remarkably, nACTs exhibited significantly enhanced oral bioavailability, longer half-life as well as extended mean retention time in rats. In addition, the impact of nACTs on P-glycoprotein (P-gp) was evaluated using the Caco-2 cell line. The results showed that both ART and nACTs reduced the efflux rate of the P-gp substrate rhodamine 123 (R123) and induced the expression of P-gp in Caco-2 cells over a range of concentrations. nACTs had certain components-deoxyartemisinin (DEART), artemisinic acid (AA), and dihydroartemisinic acid (DHAA)-that inhibited the efflux and translocation of P-gp and facilitated the reduction of ART efflux. In conclusion, A. annua extracts significantly improved the antimalarial efficacy and bioavailability compared with ART.

CAS / MDL: 8001-22-7
研究领域: 药理学 · 寄生虫学 · 植物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2019 · IF 3.375

Ultrasonic Assisted Extraction of Artemisinin from Artemisia annua L. Using Poly(Ethylene Glycol): Toward a Greener Process

Phongphat Prawang,Yongqiang Zhang,Ying Zhang,Hui Wang

Poly(ethylene glycol) (PEG), a kind of “green” medium, was used to extract artemisinin from the Chinese herb Artemisia annua L. to replace the traditional volatile and explosive solvents like petroleum ether, diethyl ether, etc. PEGs, with different molecular weights, show excellent ability for artemisinin extraction, and the extraction efficiency decreased with the increase of molecular weight. It was also demonstrated that ultrasonic irradiation could further enhance extraction efficiency compared with conventional water bath heating. Results indicate that the extraction amount of artemisinin from one gram of the leaves could reach 15.8 mg/g under the optimal conditions with ultrasonic power of 100 W, the temperature of 50 °C, time of 1 h in PEG-200, which were optimized by response surface method. Compared with Soxhlet extraction using petroleum ether (PE), the method developed here shows higher extraction efficiency (15.8 mg/g for PEG vs. 14.9 mg/g for PE process) and shorter extraction time (1 h vs. ca. 12 h). Additionally, artemisinin in the PEG solution can be recovered using resin adsorber. The results show that the recovery of artemisinin could reach almost 100% by D101 or H103 porous resin, and then the drug could be desorbed from the resin by ethanol or ethyl acetate. Moreover, the kinetic and mechanism studies of the extraction process revealed that ultrasonic irradiation could enhance mass transfer and the hydrogen bonding interactions between artemisinin and PEG further facilitate the separation of artemisinin from the leaves. This work provides an alternative process for efficient artemisinin extraction by using an environmentally benign medium with outfield intensification, which could be potentially extended to the production of other natural drugs.

CAS / MDL: 63968-64-9
研究领域: 药学 · 环境化学 · 生物技术 · 化工
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Chinese Medicine · 2025 ·Vol. 20 ·期 1 ·1-21 · IF 5.7

Artemisia annua-derived extracellular vesicles reprogram breast tumor immune microenvironment via altering macrophage polarization and synergizing recruitment of T lymphocytes

Wang Yun,Meng Lin,Su Sicheng,Zhao Yu,Hu Xiaoxian,Xu Xiaoqing,Han Chao,Luo Jianguang,Li Zhongrui

Background The immunosuppressive microenvironment and limited immune cell infiltration into the tumor bed contribute to the proliferation, metastasis, and invasion of breast cancer (BC) cells. Reprogramming the tumor immune microenvironment has emerged as a promising therapeutic target for BC, but remains challenging in clinical practice. Artemisia annua , a medicinal plant, has shown immune-enhancing and anti-tumor activities, although its potential therapeutic applications in BC remain underexplored. Methods Extracellular vesicles (EVs) were isolated from fresh Artemisia annua using gradient centrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), Zetasizer Nano ZS90, ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS), and high-performance liquid chromatography (HPLC). Single-cell RNA sequencing (scRNA-seq) analysis was performed to investigate the mechanism of AEVs on tumor growth in vivo and mRNA sequencing (mRNA-seq) was employed to further explore the mechanism of AEVs-induced polarization shift from M2-like to M1-like macrophages. In vitro and in vivo assays were conducted to assess the polarization of macrophages and recruitment of T lymphocytes into the tumor bed. Results AEVs were successfully isolated and characterized. In vivo, AEVs inhibited tumor growth by shifting macrophage polarization from the M2-like to the M1-like phenotype, and synergistically enhancing the recruitment of CD8 + and CD4 + T cells into the tumor microenvironment. AEVs activated the NF-κB signaling pathway while inhibiting the PPARγ pathway, thereby promoting the M1-like polarization of macrophages. Polarized M1-like macrophages secreted chemokines (CCL5 and CCL3), which facilitated T lymphocyte infiltration into the tumor bed. Notably, AEVs reshaped the BC immune microenvironment without inducing systemic toxicity. Conclusions AEVs from Artemisia annua efficiently reprogrammed the immune microenvironment of breast cancer by inducing macrophage polarization and enhancing T lymphocyte infiltration. This study lays the foundation for using AEVs as a potential immunotherapy for BC and highlights the medicinal value of Artemisia annua in cancer treatment.

CAS / MDL: 63968-64-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Sustainable Chemistry & Engineering · 2017 · IF 5.951

Well-Designed Hydrophobic Deep Eutectic Solvents As Green and Efficient Media for the Extraction of Artemisinin from Artemisia annua Leaves

Jun Cao,Meng Yang,Fuliang Cao,Jiahong Wang,Erzheng Su

The green and efficient extraction of bioactive compounds from plant biomass is an important area of interest in the pharmaceutical industries. Hydrophilic deep eutectic solvents (DESs) have been considered as green alternatives to conventional solvents for bioactive compound extraction. In this study, we aimed to provide a practical example demonstrating the tunability of hydrophobic DESs as designer solvents to efficiently extract bioactive compounds from plant biomass. Artemisinin, known as the only drug effective in the treatment of malaria, was chosen for extraction from Artemisia annua leaves. A hydrophobic DES named N81Cl-NBA that was tailor-made from methyl trioctyl ammonium chloride and 1-butanol at a molar ratio of 1:4 showed the highest extraction yield. With N81Cl-NBA-based ultrasound-assisted extraction (UAE), the main factors affecting the extraction yield were statistically optimized using a central composite design combined with a response surface methodology. The optimal conditions were obtained as follows: solvent/solid ratio 17.5:1, ultrasonic power 180 W, temperature 45 °C, particle size 80 mesh, and extraction time 70 min. Under these conditions, an extraction yield of 7.9936 ± 0.0364 mg/g was obtained, which was distinctly higher than that obtained using the conventional organic solvent petroleum ether. Moreover, the recovery of the target artemisinin from the N81Cl-NBA extraction solution was achieved by AB-8 macroporous resin with a recovery yield of 85.65%. N81Cl-NBA could be reused at least two times without a significant decrease in extraction yield. This study suggests that not only hydrophilic DESs but also hydrophobic DESs are truly designer solvents that can be used as green and safe extraction solvents for pharmaceutical applications.

研究领域: 药学 · 植物化学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2022 ·Vol. 23 ·期 23 ·14903 · IF 6.208

A Discovery-Based Metabolomic Approach Using UPLC-Q-TOF-MS/MS Reveals Potential Antimalarial Compounds Present in Artemisia annua L.

Henan Shi,Zhuqing Wang,Fujie Xu,Jialin Li,Jing Li,Manyuan Wang

In 1972, Nobel laureate Youyou Tu’s research team conducted clinical trials on the dried material ofArtemisia annuaL. from Beijing extracted by ether and then treated with alkali (called “ether neutral dry”), which showed that artemisinin was not the only antimalarial component contained. The biosynthesis of sesquiterpenoids inA. annuahas increased exponentially after unremitting cultivation efforts, and the plant resources are now quite different from those in the 1970s. In consideration of emerging artemisinin resistance, it is of great theoretical and practical value to further study the antimalarial activity ofA. annuaand explore its causes. The purpose of this study is to clarify scientific questions, such as “What ingredients are synergistic with artemisinin inA. annua?”, and “Are there non-artemisinin antimalarial ingredients inA. annua?”. In this paper, Beijing wildA. annuawas used as a control and two representative cultivation species ofA. annuawere selected to evaluate the antimalarial activity of the herbal medicine. The antimalarial activity of different extracts on mice was studied using the Peters’ four-day suppressive test. UPLC-Q-TOF-MS was used to obtain mass spectrum data for all samples, and a UNIFI platform was used for identification. A multivariate statistical method was used to screen the different compounds with positive correlations. The antimalarial activity of different components from the ether extract and alkali treatments was determined and antimalarial components other than artemisinin were obtained. A total of 24 flavonoids, 68 sesquiterpenoids and 21 other compounds were identified. Compounds associated with differential antimalarial activity were identified. The material basis for the antimalarial activity ofA. annuawas clarified. The antimalarial components ofA. annuainclude two categories: first, artemisinin and non-artemisinin antimalarial active components, of which the non-artemisinin antimalarial active components may include 5α-hydroperoxy-eudesma-4(15),11-diene; second, several antimalarial synergistic ingredients inA. annua, including arteanniun B, arteanniun B analogues and polymethoxy flavonoids.Keywords:Artemisia annuaL.;synergistic effect;antimalarial;UPLC-Q-TOF-MS;OPLS-DA

研究领域: 药理学 · 代谢组学 · 药物化学 · 植物科学
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TALANTA · 2018 · IF 4.244

Simple, Fast, and Sensitive detection of artemisinin in human serum and Artemisia annua using microsensor array coupled with electrochemiluminescent imaging technique

Xiao-Chong Tang,Yi Xiao,Ping Li,Lian-Wen Qi

Artemisinin is an important frontline antimalarial . Fast, accurate detection of artemisinin in human serum is of importance in monitoring its clinical pharmaceutical effect. In this work, a strategy using microsensor array coupled with electrochemiluminescence (ECL) imaging technique was developed for detection of artemisinin. The microsensor array was constructed by integrating a patterned indium tin oxide glass plate with two perforated hydrophobic paper covers. By introducing the reactant of p-aminophenylboronic acid, luminol and artemisinin into the microsensor array, artemisinin would oxidize p-aminophenylboronic acid into p-aminophenol, a product which can efficiently inhibit the ECL of luminol. ECL signals decrease linearly with the increase of artemisinin. Based on the decreased ECL signal, artemisinin can be accurately detected. A good linearity ( r  = 0.994) was observed for artemisinin detection. The detection sensitivity is 0.48 μM for artemisinin. The detection selectivity and stability were also investigated. Results show that the present method shows a good selectivity and stability towards artemisinin detection. To evaluate the applicability of the present strategy for detecting artemisinin in real samples, the artemisinin content in human serum and Artemisia annua samples were analyzed. Results demonstrated that the present strategy shows excellent selectivity with high sensitivity towards artemisinin detection in real samples.

研究领域: 分析化学 · 医学检测 · 药理学
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2022 · IF 6.056

Properties and biological activity of chitosan-coix seed starch films incorporated with nano zinc oxide and Artemisia annua essential oil for pork preservation

Kewang Zheng,Jianbing Zhang,Fan Yang,Wei Wang,Wei Li,Caiqin Qin

Edible films based on chitosan, coix seed starch (CSS), nano zinc oxide (ZnO) and Artemisia annua essential oil (AO) were obtained through solvent casting method. Physico-chemical, biological properties and structures of the edible film were analyzed and the preservation effect of it on the quality of cold-stored pork was also investigated. Fourier-transform infrared spectroscopy (FTIR) indicated that some possible intermolecular interactions could exist between film matrix and ZnO or AO. Scanning electron microscope (SEM) and thermogravimetry (TG) showed that ZnO and AO had good compatibility with the film biopolymers, no any phase separation. Results suggested that appropriate content of ZnO could enhance the film's compactness. Tensile strength (TS), barrier properties and antibacterial activities of the film was significantly enhanced with 5% ZnO was added. Incorporation of AO into the edible film decreased the TS, but increased the flexibility, barrier properties, antibacterial and antioxidant activities. When content of ZnO and AO were 5% and 8%, the physico-chemical, biological properties of the edible film could reach optimum. For pork preservation, pH, thiobarbituric acid reactive substances (TBARS), total viable count (TVC), and total volatile basic nitrogen (TVB-N) values of the pork which treated with 5% ZnO-8% AO film were significantly lowest (p ≤ 0.05) than other groups. Therefore, this edible film system has potential as food packaging materials.

CAS / MDL: 1314-13-2
研究领域: 食品科学 · 材料科学
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